POS0841 HIGH-INTENSITY INDUCTION THERAPY COMBINING TOFACITINIB, RITUXIMAB, AND PLASMAPHERESIS IN RAPIDLY PROGRESSIVE INTERSTITIAL LUNG DISEASE ASSOCIATED WITH ANTI-MDA5 ANTIBODY POSITIVE DERMATOMYOSITIS
Authors: T. Shirai, H. Sato, H. Fujii, T. Ishii
Journal: Annals of the Rheumatic Diseases (2022)

Background Rapidly progressive interstitial lung disease (RP-ILD) associated with anti-melanoma differentiation-associated protein 5 (MDA5) autoantibody (Ab) -positive dermatomyositis (DM) is one of the most life-threatening autoimmune conditions. The clinical course is very rapid, leading to death within three months after the onset of symptoms. Although triple therapy which consists of corticosteroids, cyclophosphamide, and tacrolimus has been considered as standard therapy and additional treatments including plasma exchange (PE) and rituximab (RTX) have been reported, the survival rate of patients with poor prognostic factors is still poor even if all of these treatments were applied. Recently, there exist increasing evidences regarding the efficacy of tofacitinib (TOF) in refractory DM. We have treated anti-MDA5Ab-positive RP-ILD with multiple poor prognostic factors with high-intensity induction therapy which combined triple therapy, PE, RTX, and TOF. Objectives This study aimed to investigate the therapeutic efficacy of high-intensity induction therapy for patients with anti-MDA5Ab-positive RP-ILD with multiple poor prognostic factors. Methods 31 patients who were diagnosed with anti-MDA5Ab-positive DM during 2014 to 2021 in our institution were included in this study. The clinical characteristics for poor prognosis were retrospectively analyzed, and the outcomes of high-intensity induction therapy were analyzed for the survival and adverse events. Results 17 cases were treated before the introduction of TOF. Although triple therapy with RTX, PE, or intravenous immunoglobulin (IVIG) were used, eight out of 10 RP-ILD cases with a ferritin level &gt;400 ng/mL (range, 402.5-5,831; mean, 2,342 ± 2,069) died in median 2.5 months. Poor prognosis was predicted by followings; elevated levels of serum ferritin, lactate dehydrogenase, transaminases, creatinine phosphokinase, and C-reactive protein; decrease in platelets, serum albumin, and oxygen saturation; use of oxygen; higher age; shorter disease duration to admission. The addition of RTX and PE was not enough to control RP-ILD in anti-MDA5Ab positive DM, and prevention of the initial exacerbation of ILD following induction therapy was considered to be important. Based on these observations, high-intensity induction therapy was consisted as follows; triple therapy with decreasing the dose of methylprednisolone by half from 1g to 1 mg/kg, liposteroid to suppress macrophage activity, TOF, PE, and RTX. High-intensity induction therapy was applied in eight patients (ferritin levels; range, 412.2-7,095 ng/mL; mean, 3,558±3,152 ng/mL) with multiple poor prognostic factors described above. Although deaths at two months and eight months due to ILD were observed, significant improvement of survival was documented (Figure 1). Two patients in whom RTX was not initially administered, exacerbation of ILD was observed one month later, which prompted the use of RTX. Several adverse events were observed in high-intensity induction therapy. The most common events were reactivation of cytomegalovirus, meanwhile herpes zoster was not documented. Sustained leukocytopenia and thrombocytopenia were observed in three patients, and two patients developed thrombotic microangiopathy which led to the discontinuation of tacrolimus. Fungal infections in lung were also documented. These adverse events were controllable. Figure 1. Conclusion Significant improvement of survival was observed in patients treated with high-intensity induction therapy. Meanwhile, stratification of patients for poor prognosis would be important. References None Disclosure of Interests None declared